Effect of the active ingredient of Kaempferia parviflora, 5,7-dimethoxyflavone, on the pharmacokinetics of midazolam

Ochiai, Wataru; Kobayashi, Hiroko; Kitaoka, Satoshi; Kashiwada, Mayumi; Koyama, Yuya; Nakaishi, Saho; Nagai, Tomomi; Aburada, Masaki; Sugiyama, Kiyoshi

doi:10.1007/s11418-018-1184-z

Cited by 6 publications

(4 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The results listed by Ochiai et al [48] stated that the continued ingestion of ( 88 ) isolated from K. parviflora decreases liver CYP3A expression, which in turn increased levels of compounds metabolized by CYP3As such as midazolam [48].…”

Section: Biological Activitymentioning

confidence: 99%

Recent Advances in Kaempferia Phytochemistry and Biological Activity: A Comprehensive Review

et al. 2019

View full text Add to dashboard Cite

Background: Plants belonging to the genus Kaempferia (family: Zingiberaceae) are distributed in Asia, especially in the southeast region, and Thailand. They have been widely used in traditional medicines to cure metabolic disorders, inflammation, urinary tract infections, fevers, coughs, hypertension, erectile dysfunction, abdominal and gastrointestinal ailments, asthma, wounds, rheumatism, epilepsy, and skin diseases. Objective: Herein, we reported a comprehensive review, including the traditional applications, biological and pharmacological advances, and phytochemical constituents of Kaempheria species from 1972 up to early 2019. Materials and methods: All the information and reported studies concerning Kaempheria plants were summarized from library and digital databases (e.g., Google Scholar, Sci-finder, PubMed, Springer, Elsevier, MDPI, Web of Science, etc.). The correlation between the Kaempheria species was evaluated via principal component analysis (PCA) and agglomerative hierarchical clustering (AHC), based on the main chemical classes of compounds. Results: Approximately 141 chemical constituents have been isolated and reported from Kaempferia species, such as isopimarane, abietane, labdane and clerodane diterpenoids, flavonoids, phenolic acids, phenyl-heptanoids, curcuminoids, tetrahydropyrano-phenolic, and steroids. A probable biosynthesis pathway for the isopimaradiene skeleton is illustrated. In addition, 15 main documented components of volatile oils of Kaempheria were summarized. Biological activities including anticancer, anti-inflammatory, antimicrobial, anticholinesterase, antioxidant, anti-obesity-induced dermatopathy, wound healing, neuroprotective, anti-allergenic, and anti-nociceptive were demonstrated. Conclusions: Up to date, significant advances in phytochemical and pharmacological studies of different Kaempheria species have been witnessed. So, the traditional uses of these plants have been clarified via modern in vitro and in vivo biological studies. In addition, these traditional uses and reported biological results could be correlated via the chemical characterization of these plants. All these data will support the biologists in the elucidation of the biological mechanisms of these plants.

show abstract

Section: Biological Activitymentioning

confidence: 99%

Recent Advances in Kaempferia Phytochemistry and Biological Activity: A Comprehensive Review

et al. 2019

View full text Add to dashboard Cite

show abstract

“…This suggests that KP extract induced drug interactions mediated by CYP3A inhibition in rats in vivo . Ochiai et al reported that administration of 5,7-DMF to mice for 10 days resulted in decreased expression of hepatic CYP3A, increased AUC 0-∞ and C max of MDZ, and prolonged half-life 18 ) . In contrast, in our experiments, the effect of a single KP extract treatment was examined as a condition that does not affect expression of CYP3A, and the results obtained are considered to be mediated by CYP3A inhibition.…”

Section: Discussionmentioning

confidence: 99%

“…KP extract reportedly inhibited CYP3A activity in an in vitro experiment using mouse liver microsomes 17 ) . In addition, Ochiai et al reported that administration of 5,7-DMF to mice for ten days increased the area under the serum concentration-time curve (AUC) and elimination half-life (t 1/2 ) of midazolam (MDZ), which is a probe drug of CYP3A, and decreased hepatic CYP3A expression 18 ) . However, both reports used mice and whether the same effects will also be observed in humans is unclear.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of CYP3A-mediated Midazolam Metabolism by <i>Kaempferia Parviflora</i>

et al. 2022

View full text Add to dashboard Cite

Kaempferia parviflora (KP) extract has recently attracted attention in Japan as a dietary supplement; however, there is little information regarding food-drug interactions (FDIs). The current study was conducted to clarify the FDI of KP extract via inhibition of cytochrome P450 3A (CYP3A), a typical drug-metabolizing enzyme. The inhibitory effects of KP extract and its main ingredients, 5,7-dimethoxyflavone (5,7-DMF) and 3,5,7,3’,4’-pentamethoxyflavone (3,5,7,3’,4’-PMF), on CYP3A-mediated midazolam 1’-hydroxylation (MDZ 1’-OH) activity were investigated in human liver microsomes. In addition, the effect of a single oral treatment with KP extract (135 mg/kg) on oral MDZ (15 mg/kg) metabolism was investigated in rats. Serum MDZ concentration was analyzed and pharmacokinetic parameters were compared with the control group. KP extract competitively inhibited MDZ 1’-OH activity with an inhibition constant value of 78.14 µg/ml, which was lower than the estimated concentration in the small intestine after ingestion. Furthermore, KP extract, 5,7-DMF, and 3,5,7,3’,4’-PMF inhibited the activity in a time-, NADPH-, and concentration-dependent manner. In vivo study showed that administration of KP extract to rats 2 h before MDZ significantly increased the area under the serum concentration-time curve and the maximum concentration of MDZ significantly by 2.3- and 1.9- fold, respectively ( p < 0.05). Conversely, administration of MDZ 18 h after KP extract treatment displayed a weaker effect. These results suggest that KP extract competitively inhibits CYP3A-mediated MDZ metabolism, and that this inhibition may be time-dependent but not irreversible. This work suggests an FDI through CYP3A inhibition by KP extract.

show abstract

“…Most of the phytochemical studies on K. parviflora in the 2020s have discussed the isolation and structural identification of methoxy flavones in rhizomes and the evaluation of its pharmaceutical properties [ 30 , 33 , 41 , 42 , 43 , 44 ]. In addition, the presence of phenolic glycosides [ 45 , 46 ], acetophenone [ 47 ], and terpenoids [ 15 , 48 , 49 , 50 ] has been reported from the rhizome extracts.…”

Section: Introductionmentioning

confidence: 99%

Exploring Volatile Organic Compounds in Rhizomes and Leaves of Kaempferia parviflora Wall. Ex Baker Using HS-SPME and GC–TOF/MS Combined with Multivariate Analysis

Thawtar,

Kusano,

Yingtao

et al. 2023

Metabolites

View full text Add to dashboard Cite

Volatile organic compounds (VOCs) play an important role in the biological activities of the medicinal Zingiberaceae species. In commercial preparations of VOCs from Kaempferia parviflora rhizomes, its leaves are wasted as by-products. The foliage could be an alternative source to rhizome, but its VOCs composition has not been explored previously. In this study, the VOCs in the leaves and rhizomes of K. parviflora plants grown in a growth room and in the field were analyzed using the headspace solid-phase microextraction (HS-SPME) method coupled with gas chromatography and time-of-flight mass spectrometry (GC-TOF-MS). The results showed a total of 75 and 78 VOCs identified from the leaves and rhizomes, respectively, of plants grown in the growth room. In the field samples, 96 VOCs were detected from the leaves and 98 from the rhizomes. These numbers are higher compared to the previous reports, which can be attributed to the analytical techniques used. It was also observed that monoterpenes were dominant in leaves, whereas sesquiterpenes were more abundant in rhizomes. Principal component analysis (PCA) revealed significantly higher abundance and diversity of VOCs in plants grown in the field than in the growth room. A high level of similarity of identified VOCs between the two tissues was also observed, as they shared 68 and 94 VOCs in the growth room and field samples, respectively. The difference lies in the relative abundance of VOCs, as most of them are abundant in rhizomes. Overall, the current study showed that the leaves of K. parviflora, grown in any growth conditions, can be further utilized as an alternative source of VOCs for rhizomes.

show abstract

Effect of the active ingredient of Kaempferia parviflora, 5,7-dimethoxyflavone, on the pharmacokinetics of midazolam

Cited by 6 publications

References 36 publications

Recent Advances in Kaempferia Phytochemistry and Biological Activity: A Comprehensive Review

Recent Advances in Kaempferia Phytochemistry and Biological Activity: A Comprehensive Review

Inhibition of CYP3A-mediated Midazolam Metabolism by <i>Kaempferia Parviflora</i>

Exploring Volatile Organic Compounds in Rhizomes and Leaves of Kaempferia parviflora Wall. Ex Baker Using HS-SPME and GC–TOF/MS Combined with Multivariate Analysis

Contact Info

Product

Resources

About